The long-term goal of the proposed research is to improve clinical outcomes for Hoarding Disorder (HD), a common and potentially debilitating condition that poses a severe public health burden. The PI has developed and tested a cognitive-behavioral therapy (CBT) that appears moderately effective, although there is clear room for improvement. In the present study, we propose to merge this line of research with the PI's recent NIH-supported neuroimaging research that points to specific functional abnormalities in regions of interest (ROIs) related to cognitive and affective decision- making processes. Patients with HD (n = 80) will be randomized to CBT or wait list (WL). At pre-treatment, mid-treatment, and post-treatment, patients will undergo functional magnetic resonance imaging (fMRI) during an acquiring and discarding decision-making task that has been used successfully in our previous work. In addition, patients will complete a number of laboratory tasks designed to assess decision-making capacity and impairment. A group of healthy control (HC) participants (n = 40) will also complete these measures as a normative control group. The primary aim of the proposed study is to determine the extent to which the observed patterns of neural activity in HD change following CBT. Under this aim, we predict that HD patients (vs. HCs) will show greater hemodynamic activity in ROIs associated with cognitive and affective aspects of decision-making. We further predict that HD patients receiving CBT (vs. WL) will show decreased activity in those ROIs, and will no longer differ from HCs following CBT. A secondary aim of the proposed study is to determine the relationship between change in activity in brain regions of interest and hoarding-related symptoms and impairments. We expect, that hemodynamic activity in the target ROIs will correlate with symptoms of HD and with performance on decision-making tasks; and that change in brain activity will correspond to both symptom and mechanism changes over the course of treatment. Finally, an exploratory aim is to explore, using both data-driven and model-constrained approaches, patterns of pre-treatment neural activity that predict response to CBT. We predict that among treated HD patients, pre-treatment activity in the target ROIs will correlate significantly with HD symptom change from pre- to post- treatment. This study promotes the NIMH strategic plan by identifying and integrating biomarkers and behavioral indicators associated with HD (Strategy 1.3), by focusing on the biological and behavioral moderators of response to psychosocial intervention in this population (Strategy 3.1), and using research on the biological causes of disorder to inform and develop psychosocial interventions that target core features of disease (Strategy 3.1). Results of the proposed study are expected to elucidate the neural mechanisms of successful response to CBT treatment for hoarding patients, and to set the stage for further treatment development and possible improvements in outcome for this disorder.